Obesity is excess body weight for a particular age, sex and height as a consequence of imbalance between energy intake and energy expenditure. The primary cause of obesity is either due to overeating, inadequate exercise or eating disorder, some genetic disorders, underlying illness (e.g., hypothyroidism), certain medications, sedentary lifestyle, a high glycemic diet (i.e., a diet that consists of meals that give high post-prandial blood sugar) weight cycling (caused by repeated attempts to lose weight by dieting, eating disorders), stress and insufficient sleep.
During the past 20 years, obesity among adults has risen significantly in the United States. The latest data from the National Center for Health Statistics show that 30 percent of U.S. adults of 20 years of age and older, i.e. over 60 million people, are obese. The percentage of young people who are overweight has more than tripled since 1980. More than 16% of the children and teens aged 6-19 years, that is over 9 million young people, are considered overweight. Although, the US national health objectives for the year 2010 is to reduce the prevalence of obesity among adults to less than 15%, current data indicate that the situation is worsening rather than improving. Obesity in Europe was recognized as a serious problem, with up to 27% of men, 38% of women and 3 million children are clinically obese. The obesity was not limited to developed countries, but it was rapidly becoming a problem in developing countries as well.
As per World Health Organization's (WHO) latest projections, approximately 1.6 billion adults (age 15+) were overweight and at least 400 million adults were obese globally in 2005. WHO further projects that by 2015, approximately 2.3 billion adults will be overweight and more than 700 million will be obese.
Recent studies have shown that approximately a third of variance in adult body weights result from genetic influences. Leptin, an adipocyte and placenta-derived circulating protein, regulates the magnitude of fat stores in the body leading to obesity. Gastrointestinal peptides, neurotransmitters and adipose tissue may also have an etiologic role in obesity. Obesity and adipose tissue expansion increase the risk of hypertension, type 2 diabetes, arthritis, elevated cholesterol, cancer and serious hormonal imbalances in women, leading to sterility. Obesity also increases the risk of, dyslipidemia (for example, high total cholesterol or high levels of triglycerides), gallbladder disease, osteoarthritis, sleep disorders, respiratory problems, arteriosclerosis and heart failure.
Obesity is the culmination of many underlying mechanisms. Obesity is characterized as uncontrolled adipose tissue mass in the body and recognized as the fastest growing metabolic disorder in the world. An increase in adipose tissue mass can be the result of the production of new fat cells through the process of adipogenesis and/or the deposition of increased amounts of cytoplasmic triglyceride or lipid droplets per cell. In the adipogenesis process, proliferation of preadipocytes or precursor fat cells needs to be followed by the differentiation of these cells to the mature adipocyte phenotype. Increased lipid accumulation in the mature adipocyte cells is the most important feature of obesity disorder. Peroxisome Proliferator-Activator Receptor gamma (PPAR-γ) is predominantly expressed in adipocytes and is a key determination factor for adipogenesis.
Fat is stored as triglycerides form in adipose tissue. The breakdown of this fat in fat cells into glycerol and fatty acids is known as lipolysis. The body's adrenergic system plays a major part in regulating energy expenditure and lipolysis. In this process catecholamines mobilize energy-rich lipids by stimulating lipolysis in fat cells and thermogenesis in brown adipose tissue and skeletal muscle. It is known that PPAR alpha plays an important role in regulating lipolysis through the control of lipid metabolic enzymes such as lipoprotein lipase (LPL).
Effective anti-obese therapies with satisfactory efficacy and acceptable safety have been long overdue. More importantly, anti-obese agents of natural origin with proven safety are greatly needed to control the growing menace. Many herbal and natural products containing gymnema extract, garcinia extract, or carnitine, for example are known to prevent fat accumulation through the inhibition of fat absorption, enhancement of fat decomposition, and the enhancement of fat consumption by the body. It is particularly advantageous for inhibition, amelioration and prevention of obesity if an anti-obesity action can be imparted to food products and beverages, which are ordinarily ingested.
It is therefore an object of the present invention to provide a non-toxic dietary supplement composition comprising enriched demethylated curcuminoids from Curcuma longa alone or at least two of the compounds or extracts selected from enriched demethylated curcuminoids, Moringa oleifera and Murraya koenigii and optionally containing other ingredients.
A yellow pigmented fraction isolated from the rhizomes of Curcuma longa contains curcuminoids belonging to the dicinnamoyl methane group. They are considered the most important active ingredients and are believed to be responsible for the biological activity of Curcuma longa. Though their major activity is anti-inflammatory, curcuminoids have been reported to possess antioxidant, antiallergic, wound healing, antispasmodic, antibacterial, antifungal, antitumor and anti-HIV activity as well. The major curcuminoids isolated from Curcuma longa include curcumin, demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids may be found in other botanicals in addition to Curcuma longa, such as Curcuma xanthorrhiza and Curcuma zedoaria. Curcuminoids are well known for their anti-inflammatory activity. Turmeric is one of the oldest anti-inflammatory drugs used in Ayurvedic medicine. Demethylated curcumin, a minor curcuminoid from Curcuma longa is highly potent compared to the curcuminoids. The pharmacokinetics involving the safety, toxicity, dose range and biological properties of turmeric and its components, including curcumin is known.
The anti-inflammatory properties of curcumin were shown to inhibit the 5-lipoxygenase activity in rat peritoneal neutrophils as well as the 12-lipoxygenase and the cyclooxygenase activities in human platelets. Curcumin had no significant effect on quercetin-induced nuclear DNA damage, lipid peroxidation and protein degradation and thus has the unique potential of acting as both pro- and antioxidants, depending on the redox state of their biological environment.
The Moringaceae is a single genus family with 14 known species. Of these, Moringa oleifera Lam. (syns: Moringa pterygosperma Gaertn.) is the most widely known and utilized species. The tree ranges in height from 5-12 m with an open, umbrella shaped crown, straight trunk (10-30 cm thick) with corky, whitish bark. A native of the sub-Himalayan regions of North West India, Moringa oleifera (M. oleifera) is now indigenous to many countries in Africa, Arabia, South East Asia, the Pacific and Caribbean Islands and South America. It is now being cultivated in the tropical and subtropical areas around the worldwide. M. oleifera commonly known as the ‘horse-radish’ tree (arising from the taste of a condiment prepared from the roots) and ‘drumstick’ tree (arising from the shape of the pods) and with many other vernacular names, indicating its significance around the world.
The leaves, pods, seeds, flowers, and roots of the Moringa oleifera tree are edible. The leaves have been proved by scientific research to be a powerhouse of nutritional value. It contains 7 times the vitamin C in oranges, 4 times the calcium in milk, 4 times the vitamin A in carrots and 2 times the protein in milk. Even though the tender pods, commonly known as ‘Drumstick’ are considered a prized vegetable for culinary preparations, the tender leaves are also used for curry preparation.
Moringa is one of the most useful plant used as food and in indigenous system of medicine. It also has medicinal importance in folk medicine for treatment of variety of human ailments like rheumatism, paralysis, epilepsy.
Photochemical investigations of different parts of M. oleifera on its resulted in the isolation and characterization of various chemical constituents such as flavonoids, carbohydrates, essential oils & lipids, amino acids & vitamins, proteins and glucosinolates and glucosinolates—derived hydrolysis products such as isothiocyanates, nitriles and carbamates.
Murraya koenigii, more commonly known as curry leaf, is a small tree growing up to 4-6 m tall, with a trunk up to 40 cm diameter. The flowers are small white, and fragrant. The small black, shiny berries are claimed to be edible, but their seeds are poisonous. The curry tree is native to India; today found almost everywhere in the Indian subcontinent excluding the high altitudes of the Himalayas.
Curry leaf is an essential leafy spice used in Asian cuisines for its distinct flavor. It has prominently been used a folk medicine in India and other Asian countries as an analgesic, astringent, antidysenteric, febrifuge, hypolipidemic and hypoglycemic agent. It is a powerful antioxidant and used for improvement of vision. It has also been used to treat night-blindness, and for regulation of fertility. The green leaves are stated to be eaten raw for curing dysentery, and the infusion of the washed leaves stops vomiting. The leaves, the bark and the roots of Murraya koenigii can be used as a tonic for stomachic. The green leaves are stated to be eaten raw for curing dysentery, and the infusion of the washed leaves stops vomiting. A toxicity study showed that methanolic extract was moderately toxic (LD50=316.23 mg/kg body weight) to rats. However Murraya koenigii has a history of hundreds of years of culinary usage by many cultures in the Eastern part of the globe.
The volatile low molecular compounds such as: β-caryophyllene, β-gurjunene, β-elemene, β-phellandrene, β-thujene, α-selinene, β-bisabolene, limonene, β-trans-ocimene and β-cadinene in the essential oil are mostly responsible for the characteristic aroma of curry leaves. Carbazole alkaloids, 9-carbethoxy-3-methylcarbazole 9-formyl-3-methylcarbazole and 3-methyl-carbazole and another alkaloid murrayacinine were isolated from the roots of Murraya koenigii. A quality study indicated that the fresh curry leaves obtained from the three New England states contained 9744 ng of lutein, 212 ng of alpha-tocopherol, and 183 ng of beta-carotene per gram fresh weight.
Administration of curry leaves to alloxan and STZ induced diabetic rats showed hypoglycemic and anti-hyperglycemic effect. The murraya carbazole alkaloids named murrayanine and 8,8′-biskoenigii ne showed antiosteoporotic activity. The carbazole alkaloids also showed mosquitocidal and antimicrobial activities and exhibited topoisomerase I and II inhibition activities. Curry leaf reduces blood cholesterol and glucose levels in ob/ob mice. The leaves showed potent antioxidant activity both in vitro and in vivo.
The inventors of the present invention have discovered in an unexpected and surprising manner that the enriched demethylated curcuminoids, Murraya koenigii plant extract and Moringa oleifera plant extract have a novel property, which is beneficial for weight management.
The inventors further established the fact that the compositions comprising enriched demethylated curcuminoids, an extract of Moringa oleifera and an extract of Murraya koenigii have synergism, which means the compositions or mixtures have stronger effect than the sum of the individual components.